A phase 1 clinical trial of SP16, a first-in-class anti-inflammatory LRP1 agonist, in healthy volunteers
BACKGROUND: Endogenous serine protease inhibitors are associated with anti-inflammatory and pro-survival signaling mediated via Low-density lipoprotein receptor-related protein 1 (LRP1) signaling. SP16 is a short polypeptide that mimics the LRP1 binding portion of alpha-1 antitrypsin.
METHODS: A pilot phase I, first-in-man, randomized, double blind, placebo-controlled safety study was conducted to evaluate a subcutaneous injection at three dose levels of SP16 (0.0125, 0.05, and 0.2 mg/kg [up to 12 mg]) or matching placebo in 3:1 ratio in healthy individuals. Safety monitoring included vital signs, laboratory examinations (including hematology, coagulation, platelet function, chemistry, myocardial toxicity) and electrocardiography (to measure effect on PR, QRS, and QTc).
RESULTS: Treatment with SP16 was not associated with treatment related serious adverse events. SP16 was associated with mild-moderate pain at the time of injection that was significantly higher than placebo on a 0-10 pain scale (6.0+/-1.4 [0.2 mg/kg] versus 1.5+/-2.1 [placebo], P = 0.0088). No differences in vital signs, laboratory examinations and electrocardiography were found in those treated with SP16 versus placebo.
CONCLUSION: A one-time treatment with SP16 for doses up to 0.2 mg/kg or 12 mg was safe in healthy volunteers.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
PloS one - 16(2021), 5 vom: 06., Seite e0247357 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wohlford, George F [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-Inflammatory Agents |
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| Anmerkungen: |
Date Completed 07.10.2021 Date Revised 20.09.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0247357 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM325086923 |
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| 100 | 1 | |a Wohlford, George F |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A phase 1 clinical trial of SP16, a first-in-class anti-inflammatory LRP1 agonist, in healthy volunteers |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 07.10.2021 | ||
| 500 | |a Date Revised 20.09.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Endogenous serine protease inhibitors are associated with anti-inflammatory and pro-survival signaling mediated via Low-density lipoprotein receptor-related protein 1 (LRP1) signaling. SP16 is a short polypeptide that mimics the LRP1 binding portion of alpha-1 antitrypsin | ||
| 520 | |a METHODS: A pilot phase I, first-in-man, randomized, double blind, placebo-controlled safety study was conducted to evaluate a subcutaneous injection at three dose levels of SP16 (0.0125, 0.05, and 0.2 mg/kg [up to 12 mg]) or matching placebo in 3:1 ratio in healthy individuals. Safety monitoring included vital signs, laboratory examinations (including hematology, coagulation, platelet function, chemistry, myocardial toxicity) and electrocardiography (to measure effect on PR, QRS, and QTc) | ||
| 520 | |a RESULTS: Treatment with SP16 was not associated with treatment related serious adverse events. SP16 was associated with mild-moderate pain at the time of injection that was significantly higher than placebo on a 0-10 pain scale (6.0+/-1.4 [0.2 mg/kg] versus 1.5+/-2.1 [placebo], P = 0.0088). No differences in vital signs, laboratory examinations and electrocardiography were found in those treated with SP16 versus placebo | ||
| 520 | |a CONCLUSION: A one-time treatment with SP16 for doses up to 0.2 mg/kg or 12 mg was safe in healthy volunteers | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
| 650 | 7 | |a LRP1 protein, human |2 NLM | |
| 650 | 7 | |a Low Density Lipoprotein Receptor-Related Protein-1 |2 NLM | |
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| 700 | 1 | |a Kadariya, Dinesh |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Taeshik |e verfasserin |4 aut | |
| 700 | 1 | |a Chiabrando, Juan Guido |e verfasserin |4 aut | |
| 700 | 1 | |a Carbone, Salvatore |e verfasserin |4 aut | |
| 700 | 1 | |a Mihalick, Virginia |e verfasserin |4 aut | |
| 700 | 1 | |a Halquist, Matthew S |e verfasserin |4 aut | |
| 700 | 1 | |a Pearcy, Adam |e verfasserin |4 aut | |
| 700 | 1 | |a Austin, Dana |e verfasserin |4 aut | |
| 700 | 1 | |a Gelber, Cohava |e verfasserin |4 aut | |
| 700 | 1 | |a Abbate, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Van Tassell, Benjamin |e verfasserin |4 aut | |
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